Pressure ventilation increases brain vascular prostacyclin production in newborn pigs.
Using awake, chronically catheterized newborn pigs, we measured cerebral blood flow (CBF), net cerebral vascular 6-keto-prostaglandin F1 alpha production, and cerebral metabolic rate of oxygen (CMRO2) during hypercapnia and during hypercapnia at increased mean airway pressure (Paw), both before and after treatment with indomethacin. CBF nearly doubled during hypercapnia. The hypercapnia-induced cerebral hyperemia was maintained when Paw was increased from 3 +/- 2 to 16 +/- 4 cm H2O during hypercapnia. Sagittal sinus pressure increased in proportion to the increase in Paw, and cardiac output was unchanged. Net cerebral production of 6-keto-prostaglandin F1 alpha increased from 9 +/- 1 to 15 +/- 1 ng/min/100 g tissue during hypercapnia and increased dramatically to 57 +/- 1 ng/min/100 g when hypercapnia was coupled with an increase in Paw. CMRO2 was not changed by either hypercapnia or increased Paw. After indomethacin, CBF decreased and cerebral vasodilation to hypercapnia did not occur. After indomethacin, adding increased Paw during hypercapnia dropped CBF below baseline, adversely affecting CMRO2. These results suggest that cerebral hypercapnia hyperemia requires brain prostanoid production and that when Paw is increased during hypercapnia, the contribution of prostanoids to maintaining CBF is increased. Increasing ventilation pressure during hypercapnia in piglets pretreated with indomethacin compromises CBF sufficiently to reduce CMRO2.
Mirro
R
R
Department of Pediatrics, University of Tennessee, Memphis 38163.
Leffler
C W
CW
Armstead
W M
WM
Busija
D W
DW
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D011464:Epoprostenol / Q000096:biosynthesis*; D006935:Hypercapnia / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D010101:Oxygen Consumption; D011175:Positive-Pressure Respiration; D013552:Swine
D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007213:Indomethacin